No single mechanism leading to steatosis exists; rather, a varied multitude of pathologies disrupt normal lipid movement through the cell and cause accumulation. These mechanisms can be separated based on whether they ultimately cause an oversupply of lipid which can not be removed quickly enough (i.e., too much in), or whether they cause a failure in lipid breakdown (i.e., not enough used). Failure of lipid metabolism can also lead to the mechanisms which would normally utilise or remove lipids becoming impaired, resulting in the accumulation of unused lipids in the cell. Certain toxins, such as alcohols,
carbon tetrachloride,
aspirin, and
diphtheria toxin, interfere with cellular machinery involved in lipid metabolism. In those with
Gaucher's disease, the
lysosomes fail to degrade lipids and steatosis arises from the accumulation of
glycolipids. Protein malnutrition, such as that seen in
kwashiorkor, results in a lack of precursor
apoproteins within the cell, therefore unused lipids which would normally participate in
lipoprotein synthesis begin to accumulate.
Macrovesicular steatosis Macrovesicular steatosis is the more common form of fatty degeneration and may be caused by oversupply of lipids due to obesity,
obstructive sleep apnea (OSA), insulin resistance, or
alcoholism. Nutrient malnutrition may also cause the mobilisation of fat from
adipocytes and create a local oversupply in the liver where lipid metabolism occurs. Excess alcohol over a long period of time can induce steatosis. The breakdown of large amounts of
ethanol in alcoholic drinks produces large amounts of chemical energy in the form of
NADH, signalling to the cell to inhibit the breakdown of
fatty acids (which also produces energy) and simultaneously increase the synthesis of
fatty acids. This "false sense of energy" results in more lipid being created than is needed.
Microvesicular steatosis Microvesicular steatosis is characterized by small intracytoplasmic fat vacuoles (liposomes) which accumulate within hepatocytes. It is associated with a wide variety of conditions, including
alcoholism,
drug toxicity of several medications,
delta hepatitis (in South America and Central Africa), sudden childhood death, congenital defects of fatty acid
beta oxidation,
cholesterol ester storage disease,
Wolman disease and
Alpers syndrome. == Histology ==